Cancer continues to have a huge social and economic impact. In 2011, 571,950 Americans died of cancer (˜25% of all deaths), with US cancer-associated costs of $263.8 billion: $102.8 billion for direct medical costs (total health expenditures); $20.9 billion for indirect morbidity costs (lost productivity); and $140.1 billion for indirect mortality costs (lost productivity from premature death). Lung cancers (-14% small cell lung cancer, SCLC, ˜85% non-small cell lung cancer, NSCLC) are the most common causes of cancer-related deaths in men and women; 156,940 patients died from lung cancer in 2011. The 5-yr survival for all stages combined is only 16%, regardless of progress in surgical management, radiation and chemotherapy [1]. Accordingly, there is a need in the field for compounds and methods for treating the numerous varieties of cancer.
In the development of new treatment modalities for cancer, there has been a resurgence of interest in drugs that form a covalent attachment to their target, especially with respect to drugs that are selective for their target [2].
The present invention includes a class of small molecule USP7 inhibitors, that have been identified to inhibit tumor growth by several mechanisms.